Waterpipe (WP) tobacco smoking is well-established in may parts of the world and is rapidly gaining in popularity in the United States, especially among college students. It is estimated that more than 100 million smokers smoke WP daily around the world. Both ancient lore and popular belief posit that WP smoking is less hazardous than smoking cigarettes, with the water purported to filter nicotine and toxicants. In addition, there are accessories that are being marketed with claims of reduced harm. WP is overtly advertised as a potentially reduced exposure product (PREP). Yet research addressing WP smoking and exposure to smoke emissions is scant, there are no acknowledged standards for testing WP smoking behavior or smoke emissions, there is no standard WP configuration to use for such testing, and there have been few quantitative assessments of human exposure to WP smoke. The specific aims of this research are to determine the variability in human WP smoking topography, how WP operating parameters impact the chemical and physical properties of WP smoke, how variation in WP operating parameters affect human smoking topography, and if WP accessories advertised to reduce harm result in lower levels of biomarkers of acute exposure. These aims will be accomplished by a series of experiments in which operating components of WP are systematically changed and smoking topography and select (carcinogenic) particle-bound semi-volatile organic and vapor phase organic constituents (SVOCs and VOCs) of smoke emissions are measured. Variation in particle size distribution with changes in WP configuration will also be assessed. These steps will result in establishing a "standard" WP configuration for subsequent testing. Finally, another sample of experienced WP smokers will smoke the standardized WP configuration, the standardized configuration with a charcoal filter, and the standardized configuration plus a bubble diffuser in random order. Biomarkers of acute exposure will be measured, including plasma nicotine and expired air CO boost, real time analysis of VOCs while smoking, and particle size distribution, and compared across the three WP configurations. PUBLIC HEALTH RELEVANCE: This work has public health implications in that (1) WP smoking involves two different chemistries (the burning of charcoal and heating of tobacco) possibly contributing uniquely to human pathology;(2) so little is known about human exposure to, and the health consequences of, WP smoking even though it is overtly advertised as a reduced risk method of tobacco use;and, (3) the study will establish methods and materials for the broader community of scientists to use in tests of WP smoking.